tbuckley/cabot-search huggingface dataset:
Abstract 14842: Concordance Between the Various Cardiovascular Risk Scores: Six Months Results of the Randomised Clinical Trial Evaluating Whole-Body Digital Twin Technology Enabled Precision Nutrition for Remission of Diabetes
Authors: Paramesh Shamanna, Jahangir Mohammed, Maluk Mohamed, Terrence Poon, Mala Dharmalingam, Arun Vadavi, Ashok Keshavamurthy, Suchitra Bhonsley, Mohamed Thajudeen, Sarah Mohammed, Shashank Joshi
Journal: Circulation (2022)

Introduction: The Twin Precision Treatment (TPT) intervention uses the Whole-Body Digital Twin Platform, with AI and the Internet of Things, to integrate multi-dimensional data to give precision nutrition and health recommendations via the TPT app and by coaches Methods: We compared the differences between the cardiovascular (CV) risk scores: (ASCVD (atherosclerotic cardiovascular disease) risk score, QRISK, and Framingham risk score (FRS) in the TWIN intervention arm (T) (n=203) and control group (C) (n=80) along with the changes in glycemic and extra glycemic parameters Results: Mean age (years) in T and C was 43.4 (±8.2) and 50.9 (±10.6); respectively. Mean duration of diabetes (years) in T and C was 3.7 (±2.6) and 4.7 (±2.8); respectively. There was a significant reduction in all three risk scores in T arm with glycemic and other extra glycemic parameters (Table). In the intervention arm, the mean difference in the ASCVD score (%) from baseline to 180 days was comparable in the group that achieved remission (AR) (n=170) -5.3 (±5.7, 95% CI -6.2 to -4.4) and the group that did not achieve remission (DAR) (n=33) -3.9 (±4, 95% CI -5.3 to -2.5) (p=019 ns). Similarly, the mean difference in the QRISK score (%) from baseline to 180 days was comparable in AR -3.3 (±5.1, 95% CI -4.1 to -2.5) and DAR -5.1 (±6.7, 95% CI -7.6 to -2.7), (p=0.07 ns). Mean difference in the FRS (%) from baseline to 180 days was comparable in AR -9.2 (±7.4, 95% CI -10.4 to -8.1) and DAR -7.4 (±6.9, 95% CI -9.8 to -4.9), (p=0.18 ns). On day 180 Kappa agreement between ASCVD and QRISK was 0.32, between QRISK and FRS was 0.63, and between ASCVD and FRS was 0.43. Conclusions: The significant reduction in all three CV risk scores at three months was sustained at six months. TPT yields a significant reduction in cardiovascular risk across the three risk scores and is independent of the achievement of remission of diabetes. TPT, apart from achieving diabetes remission, has independent benefits for the reduction of cardiovascular risk.
Abstract 15197: Trends in Prevalence and Treatment of Metabolic Syndrome and Individual Components by Race/Ethnicity, 1999-2020
Authors: Yuan Lu, Xumin Li, Yuntian Liu, Cesar Caraballo, Shiwani Mahajan, Daisy Massey, Erica S Spatz, Jeph Herrin, Harlan M Krumholz
Journal: Circulation (2022)

Introduction: Nationally representative data evaluating recent trends in racial and ethnic differences in prevalence and treatment of metabolic syndrome (MetS) are sparse. Methods: We evaluated 21-year trends in the prevalence and treatment of MetS and individual components in 21,602 adults, using data from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2020. We used weighted linear regression to estimate time trends and compared these trends by race and ethnicity. Results: Among participants, the mean age was 47.7 (SD, 2.2) years; 51 % were female; 78 %, 12.7%, and 9.3% were White, Black, and Hispanic. From 1999 to 2020, the prevalence of MetS as well as the prevalences of elevated waist circumference and elevated fasting glucose increased significantly for Black, Hispanic, and White individuals (P&lt;0.01 for all). The prevalences of elevated blood pressure and elevated triglyceride increased among Black individuals but did not change among Hispanic and White individuals. The use of antihypertensive, antihyperglycemic, and lipid-modifying medications also increased for all racial/ethnic subgroups. Racial/ethnic disparities in prevalence and treatment of MetS and individual components persisted throughout the study period. Compared with White individuals, Black individuals had higher use of antihypertensive medications but lower use of lipid-modifying medications (P&lt;0.01 for all). Hispanic individuals had lower use of antihypertensive medications and lipid-modifying medications (P&lt;0.01 for all). Across all racial/ethnic subgroups, less than 60% and 30% of people with medication indications received lipid-modifying and antihyperglycemic medications, respectively. Conclusions: Temporal trends suggest an increase in prevalence of MetS. There were persistent racial/ethnic disparities in use of antihypertensive, antihyperglycemic, and lipid-modifying medications among people with medication indications.
Abstract 14938: Endothelial Cell-Targeted Nanoparticle Delivery of Crispr/Cas9 Plasmid Dna Disrupts Endothelial <i>Epas1</i> in Adult Rats and Inhibits Experimental Pah
Authors: Narsa Machireddy, Jingbo Dai, Yi Peng, Shawn Trewartha, Youyang Zhao
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by obliterative vascular remodeling that leads to right heart failure and death. HIF-2α (hypoxia-inducible factor-2α) activation in lung endothelial cells is obligatory to obliterative pulmonary vascular remodeling in PAH patients and animal PAH models. Hypothesis: Endothelial cell-targeted nanoparticle can deliver plasmid DNA expressing the CRISPR/Cas9 system to disrupt Epas1 (encoding HIF-2α) selectively in endothelial cells in adult rats and inhibit PAH in monocrotaline rats. Methods: To target endothelium for robust genome editing, we developed poly(ethylene glycol) methyl ether- block -poly(lactide-co-glycolide) (PEG- b -PLGA) copolymer-based nanoparticle formulated with polyethyleneimine. A single i.v. administration of mixture of nanoparticles and plasmid DNA expressing Cas9 controlled by rat Cdh5 promoter and guide RNAs targeting Epas1 driven by U6 promoter induced highly efficient genome editing in endothelial cells in 6-weeks old SD rats. Rat Cdh5 -Cas9 plasmid DNA with scramble guide RNA were injected as a control group. One week after nanoparticle administration, the rats were injected with a single dose of monocrotaline (MCT) to induce PAH. At 4 weeks post-MCT, hemodynamic measurement of right ventricular systolic pressure RVSP and weight ratio of right ventricular versus left ventricular plus septum (RV/LV+S), an indicator of RV hypertrophy were determined. Results: Single administration of mixture of nanoparticles and CRISPR Cdh5 plasmid DNA caused diminished HIF-2α protein expression selectively in endothelial cells indicating highly efficient genome editing. Genomic editing-mediated disruption of Epas1 in endothelial cells reduced RVSP and right ventricular hypertrophy as well as obliterative pulmonary vascular remodeling in MCT-induced PAH rats. Conclusions: These findings demonstrate robust genome editing of Epas1 via EC-targeted nanoparticle delivery of CRISPR-Cas9 plasmid DNA in adult rats leading to attenuated PAH in MCT rats, suggesting EC-targeted nanoparticle delivery of genome editing system to disrupt PAH-causing gene(s) in ECs is a promising precision gene therapy of PAH in patients.
Abstract 14933: Beta1-Adrenergic Receptor Polymorphisms Modulate Receptor Processing and Function
Authors: Hanna E Tuhkanen, Jarkko J Lackman, Christoffer K Goth, Ilona Haasiomaki, Henrik Clausen, Johanna Magga, Risto Kerkela, Katrine Schjoldager, Ulla E Petaja-Repo
Journal: Circulation (2022)

The beta1-adrenergic receptor (beta1AR) is a G protein-coupled receptor that modulates the sympathetic activation of the heart. The extracellular N-terminal domain of the beta1AR, that undergoes extensive post-translational modifications, is generally overlooked as a domain influencing receptor signaling and regulation. Previously, we showed that the N-terminal domain is cleaved in an activation dependent manner, and more recently, we demonstrated that O-glycosylation inhibits the N-terminal cleavage and modulates signaling of the receptor. This suggests that processing of the N-terminal domain has a complex role in the regulation of beta1AR function. Here, we investigated the three human beta1AR (hbeta1AR) N-terminal single-nucleotide polymorphisms (SNPs) that reside close to the previously identified cleavage and O-glycosylation sites. These SNPs, S49G, R31Q and A29T, have allele frequencies of ~15%, &lt;1% and &lt;1%, respectively. The aim was to investigate if these SNPs can modulate the O-glycosylation -mediated receptor regulation. We studied the impact of the SNPs on hbeta1AR O-glycosylation, proteolytic processing and cell surface expression using cultured cell lines and isolated neonatal rat cardiomyocytes. We find that the proteolytic cleavage of the receptor is attenuated for the T29 and Q31 variants and enhanced for the G49 variant. The attenuated cleavage of T29 and Q31 variants leads to an increase in the number of full-length receptors at the cell surface. For the Q31 variant, the attenuated cleavage is caused by the disruption of the receptor cleavage site at position R31↓L32, whereas cleavage of the T29 variant is inhibited due to an additional O-glycan found at position 29. In comparison, the existing O-glycan is eliminated at position 49 in the G49 variant. We conclude that the hbeta1AR SNPs affect receptor processing via disrupting the proteolytic cleavage site at R31↓L32 (Q31 variant) or through altered O-glycosylation (T29 and G49 variants). Since the altered glycosylation/cleavage of the beta1AR variants affects the number of functional receptors at the cell surface, it can offer new strategies for drug design and help in understanding the mechanism for the decreased cardiomyocyte beta1AR density in heart failure.
Abstract 14956: Extensive Cardiac Involvement in Laminopathies Diagnosed in Pediatric-Aged Patients: A Single Center Study
Authors: Emily A Hayes, Lydia K Wright, Robert Gajarski, Kan N Hor, Linda Cripe, Naomi J Kertesz, Deipanjan Nandi
Journal: Circulation (2022)

Introduction: Lamin A/C ( LMNA ) gene mutations result in a heterogeneous group of inherited conditions termed laminopathies. Cardiac manifestations of laminopathies include atrial and ventricular arrhythmias, atrioventricular conduction disorders, and cardiomyopathy, with or without skeletal muscle involvement. Because this disease is rare and typically presents in adulthood, pediatric data is limited. Methods: We identified patients &lt; 18 years with genetically confirmed mutations in LMNA followed at our center between 2003 and 2021. Clinical phenotypes along with cardiac test results were retrospectively catalogued. Results: We identified 12 patients with a median age of 5 years at diagnosis (IQR 4-11 years) with a LMNA mutation. Nine (75%) patients were male and 10 (83%) had associated skeletal muscle involvement. Of the 12 patients, 10 (83%) developed cardiac manifestations over a median follow up period of 111 months (IQR 91-116 months). Seven patients (58%) had documented arrhythmias (AV block, ventricular/atrial tachycardias) and 3 (25%) underwent pacemaker and/or implantable cardiac defibrillator placement. Three (25%) patients were diagnosed with cardiomyopathy with 1 (8%) requiring a ventricular assist device and 1 (8%) requiring continuous intravenous inotropes and subsequent transplant. Three (25%) patients died during the study period, one awaiting transplant, one from complications post-transplant, and one from non-cardiac causes. Conclusions: Cardiac involvement, specifically cardiomyopathy and progressive conduction system abnormalities, were common in pediatric patients with LMNA mutations. Early genetic diagnosis of laminopathies followed by frequent surveillance for dysrhythmia and dysfunction is necessary for more timely initiation of advanced cardiac therapies to prevent adverse events. More comprehensive phenotype-genotype correlation is strongly needed.
Abstract 15227: Decreased Left Atrial Emptying Fraction is Associated With Increased Odds of Diagnosing Atrial Fibrillation Within 1 Year of ESUS
Authors: Ravi S Shah, Joseph Raco, Ryan Williams, Nathaniel McConkey, David Foley, Kevin Mills, Emma Hegwood, Kelly Jia, Ankit Maheshwari
Journal: Circulation (2022)

Introduction: A significant proportion of patients with embolic stroke of unknown source (ESUS) are subsequently diagnosed with atrial fibrillation (AF). Left atrial myopathy characterized by mechanical left atrial dysfunction has been associated with development of AF. Hypothesis: Decreased left atrial emptying fraction (LAEF) is independently associated with AF in patients with ESUS. Methods: Patients admitted at a tertiary care medical center for ESUS treated with implantable loop recorders from 2015-2022 were included. Patients were excluded for lack of an interpretable transthoracic echocardiogram during sinus rhythm and electrocardiogram with 6 months of ESUS. Patients were also excluded for lack of clinical follow-up. Co-variates (table) were ascertained from chart review. LAEF was calculated by Simpson’s method of discs. Results: 153 patients were included. The mean(standard deviation) LAEF of patients who developed and did not develop AF within 1 year post ESUS was 48.0%(17.0%) and 57.6%(13.1%), respectively (P&lt;0.001). The odds of diagnosing atrial fibrillation within 1 year post ESUS were 7.18-fold greater in patients with LAEF&lt;40%. Conclusions: LAEF is independently associated with increased odds of AF within 1 year post ESUS. Future research is needed to validate these findings.
Abstract 15: Hypoxia As Therapy For Mitochond​Rial Injury Following Cardiac Arrest
Authors: Lin Piao, Yong-hu Fang, Rongxue R Wu, Stephen L Archer, Willard W Sharp
Journal: Circulation (2022)

Introduction: Mitochondrial injury occurs following cardiac arrest (CA) and contributes to myocardial stunning and anoxic brain injury. Hypoxia has been proposed as a therapeutic strategy for neurodegenerative diseases associated with mitochondrial respiration defects, but its benefits in the post-CA setting remain unexplored. Here, we hypothesized mild hypoxia as therapy for post-CA mitochondrial injury. Methods and Results: Mice underwent brief asystolic CA (12 min) followed by cardiopulmonary resuscitation (CPR). One hour following successful CPR, mice were randomized to receive a brief episode (6 hours) of hyperoxia (33% O 2 ), normoxia (21% O 2 ), or hypoxia (10% O 2 ) in an environmental chamber. Post exposure, the mice were returned to room air (21% O 2 ). Hypoxia improved myocardial fractional shortening compared to normoxia and hyperoxia (Hypoxia: 45.6±2.3 %, Normoxia: 40.0±0.8 %, Hyperoxia: 29.0±4.0 %, n=5, P&lt;0.05, respectively). Hypoxia also elevated neurological scores (Hypoxia: 8.4±1.3, Hyperoxia: 5.6±1.2, n=5, P&lt;0.05) 48 hours post CA compared to hyperoxia. Ten-day survival was prolonged by hypoxia (Hypoxia: 87.5 %, Normoxia: 62.5 %, Hyperoxia: 12.5 %, n=10, P&lt;0.05, respectively). Hypoxia also improved mitochondrial function (28% increase in basic oxygen consumption and 49% increase in ATP-related oxygen consumption, n=3, P&lt;0.05, respectively) and a 20% decrease in ROS production (n=6, P&lt;0.05) compared to normoxia. Conclusion: This study has two important findings: First , we demonstrate that oxygen availability in the early post-CA period is a critical determinant of long-term post-CA outcomes. Second , we show that mild hypoxic therapy in the early post-CA period improves early mitochondrial function and long-term post-CA outcomes. These findings reveal an important oxygen-dependent therapeutic window following resuscitation from CA that has implications for post-CA critical care.
Abstract 14949: Wear Time, Frequency of and Time to First Atrial Fibrillation Detection in Patients With a History of Stroke
Authors: Purvee Parikh, Grant Gillstrom, Vincent Norlock, CJ Grigoriadis, Alexandria Dunn, Manish Wadhwa
Journal: Circulation (2022)

Introduction: Telemetry monitoring following cryptogenic stroke (CS) is routinely undertaken to rule out atrial fibrillation (AF) as a stroke source. In patients with stroke of known etiology, AF may represent an alternate mechanism for the incident stroke and predicate anticoagulation. Irrespective of classification, a potential limitation of post-stroke monitoring is the patients’ ability to wear an ambulatory monitor for an extended timeframe. Aim: Identify mobile cardiac outpatient telemetry (MCOT, Philips BioTel Heart) monitor wear time, frequency of AF detection, and time to first AF diagnosis in patients with any history of stroke. Methods: A retrospective review of 7,426 patients prescribed 30-day MCOT with ICD-10 diagnosis codes starting with I63 (cerebral infarct, unspecified) was conducted. Data from 2021 was analyzed for MCOT monitor wear time, occurrence of any AF, and time to first AF detection. Monitor wear time was defined as the time from the first to the last telemetry transmission. Results: The percentage of patients with MCOT monitor wear time of 5, 10, 15, 20, 25 and 30 days was 93%, 87%, 82%, 76%, 67% and 44%, respectively. In this cohort, 748 patients (10.1%) were identified with any AF. Of these patients, the first AF detection occurred in 33% (3.3% of total) in days 1-5 of monitoring, 20% (2.0%) in days 6-10, 15% (1.5%) during days 11-15, 14% (1.4%) during days 16-20, 9% (0.9%) during days 21-25, and 9% (0.9%) during days 26-30. Interestingly, 4% of AF detection (0.4% total) occurred on days 29-30. Conclusions: Patients with cerebral infarcts are capable of adhering to extended MCOT wear times, and 10% of patients with any history of stroke demonstrated AF when prescribed MCOT for 30 days. While most patients had first AF detection within 15 days, 32% of patients had first AF detection between days 16-30. These findings suggest that patients with any history of stroke, regardless of etiology, may benefit from extended duration telemetry monitoring.
Abstract 14764: Cardiac Cta Utilization for Chest Pain Stratification Increased During and After the Covid-19 Pandemic: Experience of a Latin-American Center
Authors: German J Medina-Rincon, Sebastian Gallo, Maria Daniela Valderrama Achury, Joaquin Castañeda, Dickens Abigail Montanez, Gabriel Salazar Castro, Claudia Gutierrez, Victor Marín, Claudia Patricia Jaimes Castellanos, Julian Francisco Forero, Hector Medina
Journal: Circulation (2022)

Introduction: During the COVID-19 pandemic, stratification of patients with chest pain with low-to-moderate probability of CAD (LMCP) became problematic due to fear of infection. We analyzed the impact in volume trends of modalities for stratification in these patients -including stress echocardiography (S-TTE), cardiac computed tomography (CCT), and single-photon emission CT (SPECT)- before, during, and after the pandemic Hypothesis: Usage of CCT increased during the COVID-19 pandemic due to the lower exposure of patients, during this test, to healthcare personnel. Methods: R etrospective chart review conducted between 2019 and 2021. We defined 3-time frames: pre-pandemic period (1/1/2019-12/31/2019), pandemic period (1/1/2020-12/31/2020), and post-pandemic period (1/1/2021-12/31/2021). The study included data of all 3 mentioned imaging modalities. Results: Our cohort included 19,637 LMCP patients evaluated using 1,369 CCTs (7%), 2,380 S-TTEs (13.6%) and 15,588 SPECTs (79.4%) -Fig 1a-. During the pre-pandemic period, CCT studies corresponded to 3.0%, while S-TTE and SPECT corresponded to 14.7% and 82.4%, respectively. In the post-pandemic period, CCT studies corresponded to 9.8%, while S-TTE and SPECT corresponded to 12.3% and 77.9%, respectively. An upward variation was observed regarding the utilization of CCT in the post-pandemic period compared to the pre-pandemic period (p&lt;0.001), and a downward change was observed in S-TTE when the post-pandemic period was compared with the pre-pandemic period (p&lt;0.001) -Fig 1b-. Conclusions: Since the beginning of the COVID-19 pandemic, the utilization of SPECT and s-TTE in LMCP patients decreased compared to the pre-pandemic period. In the post-pandemic period, both tests increased in use although their volumes are lower compared to the pre-pandemic period. Conversely, CCT had a linear increase since the beginning of the pandemic and this pattern has extended to the post-pandemic period.
Abstract 14944: Comorbid Obesity in Symptomatic Peripheral Artery Disease: A Modifiable Factor Associated With Health Status
Authors: Lindsey Scierka, poghni A peri-Okonny, Carlos Mena-Hurtado, Kensey Gosch, John Spertus, Robert Fitridge, Patrick W Vriens, Sabita Soedamah-Muthu, Kim G Smolderen
Journal: Circulation (2022)

Introduction: Obesity is a modifiable risk factor for peripheral artery disease (PAD). While highly prevalent, the association between obesity and health status outcomes in PAD has not been studied. We aim to summarize obesity management and its association with health status in patients with PAD. Methods: We conducted a longitudinal cohort study of patients with symptomatic PAD from the international multicenter PORTRAIT registry. Body mass index (BMI) was analyzed continuously (per 10kg/m2) and categorically as underweight (BMI &lt; 18.5 kg/m 2 ), normal weight (BMI 18.5 - 24.9 kg/m 2 ), overweight (BMI 25 - 29.9 kg/m 2 ) and obesity (BMI &gt; 30 kg/m 2 ). Obesity management strategies included diet or weight counseling and anti-obesity medications. Disease-specific health status was assessed with the Peripheral Artery Questionnaire (PAQ) (range=0-100, higher scores indicate better health status). Linear regression models examined the association between obesity and both baseline and 12-month PAQ summary scores. Results: Obesity was present in 37% (370/989) of patients (mean age 68.0 + 9.1 years, 40.1% female). No patients received anti-obesity medications. Weight and/or diet counseling were prescribed in only 12% of overweight and in 21% of patients with obesity. BMI (per 10 kg/m 2 ) was associated with worse PAQ summary scores at baseline (-5.7, 95% CI -8.0 to -3.5, p &lt;0.01) and 12 months (-7.8, 95% CI -12.3 to -3.4, p &lt;0.01) in unadjusted and models adjusting for medical comorbidities and PAD-associated factors. This was consistent when obesity was compared categorically to normal/overweight at baseline (mean difference = -7.2, 95% CI -10.4 to -4.1, p&lt; 0.01) and at 12 months (-7.4, 95% CI -11.4 to -3.5, p&lt; 0.01). Conclusions: Obesity is a potentially modifiable comorbidity in PAD that is currently under addressed and a strong correlate of PAD-specific health status following PAD diagnosis and treatment.